such as probenecid, bucolome, and benzbromarone (approved in August 1954, December 1966, and August 1978, respectively). ****************************************************** 2. Data relating to quality 2.A Summary of the submitted data 2.A.(1) Drug substance **************************************************************************************************************************************. 2.A.(1).1
baseline.Intervention(s), exposure(s)xanthine oxidoreductase inhibitors: allopurinol, febuxostat, topiroxostatComparator(s)/controluricosuric agents: probenecid, bucolome, benzbromarone, dotinurad, lesinurad, sulfinpyrazoneMain outcome(s)The primary efficacy endpoint will be change in eGFR.Measures of effectMean difference in annual absolute or relative change in eGFR (mL/min/1.73m2) between randomised
The effect of bucolome, a CYP2C9 inhibitor, on the pharmacokinetics of losartan. Losartan, a selective angiotensin receptor antagonist, is mainly metabolized by CYP2C9 to an active carboxylic acid, E3174, which is pharmacologically more potent inhibitor than the parent compound. We evaluated the effect of bucolome, a CYP2C9 inhibitor, on the pharmacokinetics of losartan and E3174, which were measured by high performance liquid chromatography in human volunteers and rats. A randomized crossover design study with two phases was done in the volunteer study. In the first phase, the volunteers received losartan 25 mg alone orally (LOS group), and, in the second phase, losartan 25 mg was given after repeated oral administration of 300 mg bucolome for 7 days (LOS+BUC group). In the LOS group
The stereoselective effects of bucolome on the pharmacokinetics and pharmacodynamics of racemic warfarin. The objective of this study was to investigate the stereoselective influence of bucolome on the pharmacokinetics and pharmacodynamics of warfarin in Japanese inpatients with heart disease. Thirty patients were administered a fixed-maintenance dose of warfarin alone once a day for at least 7 days. The other 25 patients were concomitantly administered warfarin and a 300 mg dose of bucolome once a day, and blood samples were collected on days 1, 4, 7, 14, or 21 after administration of bucolome. Serum concentration of warfarin enantiomers was measured by a chiral reversed-phase HPLC-ultraviolet detection method. The PT-INR was used as a measure of the pharmacodynamic effect of warfarin
Risks and benefits of combined use of bucolome and warfarin in anticoagulation therapy. Although bucolome has been used empirically to enhance and stabilize warfarin action in some institutes, the clinical risks and benefits of this combination are unclear. In the present study, warfarin monotherapy (WM) and bucolome combination (BC) therapy were compared in anticoagulation therapy.One hundred and ninety-five patients indicated for anticoagulation therapy were randomly assigned to WM (n = 98) or BC (bucolome 300 mg/day, n = 97). The dosage of warfarin was optimized in each patient to maintain the international normalized ratio (INR) level in the appropriate zone, ie, 1.6-2.6 for lower risk and 2.0-3.0 for higher risk patients. The clinical characteristics, clinical events, and time
Danger of bucolome in infants with hyperbilirubinaemia. Experimental evidence. Effects of bucolome on congenitally jaundiced Gunn rats were examined. Plasma total bilirubin level fell immediately after a single injection of bucolome and the lowered level persisted for more than 6 hours. Plasma unbound-bilirubin level and cerebellar bilirubin content increased simultaneously with the drop in total plasma bilirubin level. Kernicterus was observed in the brains of the treated rats 6 hours after the treatment. LD50 of the drug in jaundiced rats was about 37 mg/kg, about one-tenth of the value in nonjaundiced rats. It is suggested that bucolome displaces bilirubin from albumin, transferring bilirubin from blood into tissues including the brain, and resulting in kernicterus. The use of bucolome
Bucolome in prevention of hyperbilirubinaemia in preterm infants. Fifty preterm babies were randomly assigned to a group given oral bucolome (30 mg/kg per day for 5 days) and a control group. Serum bilirubin levels of the treated infants from day 4 onwards were consistently lower than those of the control infants. 3 of the 25 control infants (but none of the 25 treated infants) had bilirubin levels greater than 18 mg/100 ml (308 mumol/l) and required exchange transfusion. No sedation or drowsiness was observed in the infants given bucolome, and though the drug caused some vomiting, weight gains were unaffected.
* (10) Patients who receive any of the following medications for the treatment of hyperuricemia within 1 month prior to enrollment Allopurinol, benzbromarone, probenecid, bucolome, topiroxostat, or febuxostat * (11) Patients who start, modify the dose of, or discontinue any of the following medications within 1 month prior to enrollment Losartan, irbesartan, fenofibrate, thiazide diuretics, or loop
times the upper limit of normal. 6. Patients on any of the following medications at enrollment Mercaptopurine hydrate, azathioprine, vidarabine, or didanosine. 7. Patients who receive any of the following medications for the treatment of hyperuricemia within 1 month prior to enrollment Allopurinol, benzbromarone, probenecid, bucolome, topiroxostat, or febuxostat. 8. Patients otherwise judged
urate-lowering therapy. (allopurinol, probenecid, bucolome, febuxostat) 2. History of hypersensitivity to febuxostat. 3. Current treatment with mercaptopurine, azathioprine, pyrazinamide, or ethambutol. 4. Participant in an another clinical trial within the past 4 weeks. 5. Judged to be unsuitable as a subject by the attending physician.After two months , the patient will be reassessed regarding:A /dL or more. * Stable clinical condition (no hospitalization in the previous 3 months) * Informed consent in accordance with the Declaration of Helsinki.Exclusion Criteria: * Current urate-lowering therapy. (allopurinol, probenecid, bucolome, febuxostat) * History of hypersensitivity to febuxostat. * Current treatment with mercaptopurine, azathioprine, pyrazinamide, or ethambutol. * Participant